Expert Opinion on Therapeutic Patents最新文献

Introduction: The KDM4 family of histone demethylases, characterized by a conserved JmjC catalytic domain, comprises six subtypes: KDM4A - F. Aberrant expression of these enzymes has been associated with tumorigenesis across various malignancies, highlighting their potential as therapeutic targets in oncology. To date, a series of KDM4 inhibitors have been developed, among which TACH101 is undergoing clinical evaluation for cancer treatment.

Areas covered: This review provides a comprehensive overview of the patent literature on KDM4 inhibitors, derived from a systematic search utilizing the Cortellis Drug Discovery Intelligence database. A total of 17 patent applications, published within the period from June 2014 to May 2025, were identified and critically analyzed.

Expert opinion: Significant progress has been achieved in the development of KDM4 inhibitors; however, most current compounds continue to face major challenges, including poor membrane permeability, limited cellular potency, and low isoform specificity. Strategies such as designing inhibitors with novel scaffolds, developing covalent inhibitors, advancing protein degraders, and targeting non-catalytic domains may provide viable solutions to these limitations. In addition, the physiological and pathological roles of KDM4 remain insufficiently characterized. Further in-depth investigations into the biological functions of KDM4 will be essential to guide the rational design and facilitate the clinical translation of KDM4-targeted therapeutics.

Introduction: DNA Polymerase theta (Polθ), a critical multifunctional DNA repair enzyme in the alternative non-homologous end joining (alt-NHEJ) pathway, has recently emerged as a new promising synthetic lethal target for homologous recombination (HR) deficient cancers. Since the first-in-class Polθ polymerase inhibitor entered clinical trials in 2021, this field has witnessed explosive growth in interest, underscored by a surge in Polθ inhibitor patents and nine candidates progressing to clinical trials.

Areas covered: This comprehensive patent review focuses on structural features and biochemical profiles of both Polθ inhibitors reported between 2019 and 2025, leveraging patents retrieved from the databases of World Intellectual Property Organization (WIPO), United States Patent and Trademark Office (USPTO), Cortellis Drug Discovery Intelligence, and China National Intellectual Property Administration (CNIPA).

Expert opinion: The rapid progress of Polθ inhibitors highlights their potential as a synthetic lethal strategy for HR-deficient cancers. Recently, an increasing number of patents and articles on inhibitors targeting Polθ have been published. At present, a total of nine Polθ inhibitors are under study in early clinical trials. Artios' Polθ inhibitor ART6043 has excellent clinical data. The results of these trials will influence the future development of Polθ inhibitors for HR-deficient cancers.

Introduction: Lysine demethylases (KDMs) are crucial epigenetic regulators that modulate gene expression via demethylation of histone and non-histone proteins, playing a pivotal role in cancer progression. Dysregulation of KDM activity, particularly in KDM1A, KDM4, KDM5, and KDM6, has been linked to several cancers, including leukemia and breast, lung, and prostate cancers, leading to the emergence of KDM inhibitors (KDMi) as promising therapeutic agents. These inhibitors target KDMs by mimicking cofactors, chelating metal ions, or competing with histone substrates to disrupt demethylation. Some of the most studied KDMi are those targeting KDM1A.

Areas covered: In this review, we critically explore the complex roles of KDMs in cancer, provide a detailed overview of patents describing KDMi published from 2015 to the present, and assess European clinical trials investigating KDMi developed for cancer therapy.

Expert opinion: Despite the promising potential of KDMi, their clinical development is hampered by significant challenges including safety concerns, suboptimal patient enrollment, and difficulties in optimizing dosing regimens and identifying reliable biomarkers. Future research must focus on refining dosing protocols, discovering predictive biomarkers, and developing effective combination therapies to maximize patient outcomes, ultimately realizing the full promise of KDMi in cancer treatment.

Introduction: Sirtuins have gained significant prominence in scientific research due to their involvement in a wide array of biological processes, including DNA repair, genome stability, transcription modulation, and signal transduction. Dysregulation of their function has been implicated in various pathologies, including cancer, where sirtuins exhibit context-dependent effects. Consequently, the development of sirtuin inhibitors and activators remains an exceptionally important field of research, focusing on the design of selective modulators targeting individual sirtuin isoforms.

Areas covered: This review includes the patents regarding sirtuin modulators released from 2020 to 2024 and provides a concise overview of the most relevant modulators developed so far. Relevant patents were systematically identified through comprehensive searches in PubMed (https://pubmed.ncbi.nlm.nih.gov), Google Patents (https://patents.google.com), and Espacenet (https://worldwide.espacenet.com).

Expert opinion: Sirtuin modulators are pivotal in addressing aging, metabolism, cancer, and neurodegeneration. Sirtuins regulate key cellular processes like DNA repair, genome stability, and mitochondrial function. Activators show promise in mitigating many age-related diseases such as type 2 diabetes and neurodegeneration. Inhibitors demonstrate efficacy in oncology and neurodegenerative conditions. Advances in PROTAC technology enable selective degradation of specific isoforms, enhancing therapeutic precision. With progress in drug design and high-throughput screening, sirtuin modulators hold immense potential to revolutionize treatments for complex medical challenges.

Introduction: The hydroxamic acid-based histone deacetylase (HDAC) inhibitors play a crucial role as anticancer chemotherapeutics. It controls cellular pathways and epigenetically modifies gene expression, making them important for tackling the complicated character of cancer etiology.

Areas covered: The action of current HDAC inhibitors on different target proteins and multiple-cancer cell lines are studied. The study underlines a comprehensive summary of different compounds published as patents from 2020 to 2024 and retrieved from Google patents, paying special attention to their structural differences and possible applications in cancer treatment. It stands out in today's scenario by providing structure-activity relationships (SAR) and mechanistic insights for heterocyclic scaffold-like pyrimidine, quinazoline, oxadiazole, thiadiazole, thiazole, piperazine, pyridine, indole and chromane rings used in the design of HDAC inhibitor.

Expert opinion: Results reveal significant development in the synthesis of selective HDAC inhibitors with IC₅₀ values in the nano and micromolar range, exceeding conventional inhibitors as vorinostat. Dual-targeting approaches have also evolved as sensible substitutes using molecules that improve treatment efficacy while reducing side effects. Thorough investigation on SAR across various heterocyclic scaffolds benefits future drug development projects, aimed at improving selectivity and minimizing side effects in cancer treatment.

Introduction: Among the different topoisomerases, essential enzymes that play an important role in DNA processes such as replication and transcription, type I enzymes are targets of particular clinical importance for anticancer and antiparasitic drugs. Bearing this in mind, in the last 5 years specific inhibitors, both poison and suppressor types, have been patented for this target.

Areas covered: This review covers the patent literature on topoisomerase 1 inhibitors and their application published between late 2020-present.

Expert opinion: TOP1 inhibitors are being used in combination with synergistic therapies within a multimodal approach, including targeted therapies, adaptive immunotherapy, and the blockade of DNA repair mechanisms. Advances in drug delivery systems, especially antibody-drug conjugates (ADCs), are revolutionizing chemotherapy by enabling localized and tumor-specific drug release. In addition to traditional inhibitors like irinotecan and topotecan, new agents such as deruxtecan and govitecan have been approved, expanding therapeutic options. Moreover, small new molecules with more promising clinical potential are being developed.

Introduction: The SARS-CoV-2 main protease (Mpro, also known as 3CLpro or nsp5) is essential for viral replication. As there are no close human homologs, it represents an attractive and specific target for antiviral therapy against COVID-19. Its well-defined active site and conserved substrate specificity have enabled structure-guided drug design with high precision.

Areas covered: This review examines the patent landscape for small-molecule inhibitors of SARS-CoV-2 Mpro published between 2020 and early 2025. Compounds were grouped by scaffold type and mechanism of action, covering covalent and non-covalent inhibitors, orthosteric and allosteric binders and unique modalities such as PROTACs. Clinically advanced agents including nirmatrelvir, ensitrelvir, simnotrelvir, zevotrelvir and leritrelvir are highlighted alongside structurally novel leads and broad-spectrum candidates.

Expert opinion: A number of Mpro inhibitors have progressed into preclinical and clinical stages, underscoring the rapid advancement in this field. The accumulation of structural knowledge, chemical diversity and mechanistic insight has laid a robust foundation for future antiviral development and may further enhance the utility of Mpro inhibitors against evolving coronaviruses.

Introduction: The transcription enhancer associated domain (TEAD) family has been well documented for its roles in modulating cancer development, primarily through interactions with its two co-activators: yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Although TEAD was first reported more than two decades ago, no therapeutic compounds directly targeting this protein or its interaction with YAP/TAZ are currently available or in late-phase clinical development. This underscores the need for continued exploration of novel strategies for the molecular design of targeted therapies, to which updated patent reviews are expected to make a considerable contribution.

Areas covered: This review evaluated the Patent Cooperation Treaty (PCT) patents claiming TEAD - YAP/TAZ inhibitors published between 1 January 2022 and 30 June 2025, and provides opinions on strategies for the development of TEAD - YAP/TAZ inhibitors.

Expert opinion: Over the past 3 years, there has been a marked increase in the number of PCT patents claiming structurally diverse TEAD - YAP/TAZ inhibitors, including filings by potentially new players. This trend highlights the growing recognition of the TEAD - YAP/TAZ axis as an attractive strategy for the development of new drugs, particularly for anti-cancer therapeutics.

Introduction: Benzoxaborole is a boron-based heterocyclic scaffold with remarkable potential in medicinal chemistry. Its unique chemical structure and compatibility with biological systems have enabled the development of innovative drug candidates. Benzoxaborole derivatives exhibit diverse biological activities, including antibacterial, antifungal, antiparasitic, antiviral, anticancer, and anti-inflammatory effects, making them valuable in addressing various medical challenges.

Areas covered: This manuscript reviews the medicinal chemistry literature and patent landscape from 2019 to 2024, focusing on the therapeutic potential of benzoxaborole-based compounds.

Expert opinion: Benzoxaboroles are gaining recognition as a versatile and innovative class of therapeutics with strong potential in infectious diseases, oncology, and inflammatory conditions. Their unique boron-containing scaffold enables diverse biological interactions and favorable pharmacokinetic properties. While clinical data are still emerging, early results and robust patent activity suggest significant therapeutic value. Advances in synthetic methods, targeted delivery, and computational design are accelerating their development. With continued focused research and strategic clinical validation, benzoxaboroles are well-positioned to address pressing medical challenges, particularly antimicrobial resistance, and could become an integral part of future treatment paradigms across multiple therapeutic areas.

Introduction: The mitogen-activated protein kinase (MAPK) pathway also known as the RAS/RAF/MEK/ERK pathway is a vital intracellular signaling cascade that regulates apoptosis, differentiation, proliferation, and signal transduction.

Area covered: This review focuses on the critical role of ERK1/2 in the MAPK pathway and its implication in various cancers. It presents a detailed analysis of ERK1/2 inhibitors currently undergoing clinical evaluation, along with recently patented ERK1/2 inhibitors. The data were compiled by systematically searching databases including SciFinder, PubMed, Scopus, Google Scholar, and Google Patents using the keyword 'ERK' for the period 2019 to the present.

Expert opinion: Since 2019, several heterocyclic ERK1/2 inhibitors have shown promise in overcoming resistance within the MAPK cascade. However, detailed investigations into mutant versus wild-type ERK1/2 binding dynamics remain sparse, and the development of non-traditional approaches like PROTAC-mediated ERK degradation is still in its nascent stage. To successfully transition ERK1/2 inhibitors from bench to bedside, several strategic directions must be prioritized. First, overcoming resistance remains a critical challenge. Future ERK inhibitors must effectively target downstream components. Second, there is a pressing need to move beyond traditional ATP-competitive inhibitors. In addition, the pharmacological properties of ERK-targeting agents to enhance clinical efficacy and safety.